Horizontal gene transfer

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Genes are a precious commodity and if an organism evolves the genetic recipe that enables it to do something a bit special, other organisms often, through various mechanisms, acquire the same genetic know-how so that they too can benefit. We had thought that this gene swapping occurred mainly between just a few species or close relatives at a time. But now, Vanderbilt scientist, Seth Bordernstein, has discovered a gene that began life in bacteria-infecting viruses, called phages, and has since been traded right across the tree of life - from archea, to fungi, plants, and even people...

Seth - So, this gene is part of a lysozyme family. Technically, it's called the GH25 muramidase and it's designed to cut open the cell wall of bacteria. And particularly, the main component of the cell wall of bacteria which is called peptidoglycan. These molecules are actually used by bacteria when they divide and they make two cells, they cut open their cell wall. But other organisms have hijacked these kinds of molecules to kill bacteria. Viruses will use these types of molecules to break open their bacterial cells that they inhabit. In this case, we ended up finding that the other domains of life, Archaea, in particular, were using this particular molecule to also kill bacteria and this is something that hadn't been discovered.

Chris - Now you've got something of a chicken and egg situation though, haven't you? Because the big question must be, "Well. Which of these came first?", "Where did it start?", and then, "Where did it get into all these different parts of the tree of life along the evolutionary pathway?"

Seth - What's so clear in our case is that the only archaea that has this particular gene and makes this lysozyme lives at the bottom of the ocean near boiling vents and no other archaea in the sequence data bases have this gene. So, it's absolutely clear that this gene was horizontally transferred from bacteria, where the gene is more common, into archaea. The same thing can be said for the plant version of this gene. There are no other plant genomes on the data bases that have this gene. More exciting to us was the fact that we could guess what types of interactions led to the exchange of these genes. So, it turns out that bacteria that live with archaea at the bottom of the ocean were the likely source of these genes, and we can show that through sequence comparisons. And soil bacteria were the likely donor to give these genes to plants and fungi.

Chris - Did the viruses then steal it because they were naturally infecting the bacteria and ended up with those genetic elements finding their way into the virus and they were a useful effector. So, the virus clung onto them.

Seth - That's probably correct. In the bacterial world, viruses are constantly exchanging DNA with bacteria and vice versa. There's almost a lawless exchange of genetic information among bacteria and viruses. So, this is a very common phenomenon - horizontal gene transfer. It's not as common in archaea and eukaryotes. And moreover, what we found was the same gene had been transferring independently across the diversity of life. That's really what's new here, is sort of opening up the limits of horizontal gene transfer.

Chris - And what are the implications of this? Do you think that this is a lot broader and a lot more common than we had anticipated? And how might this inform our understanding of horizontal gene transfer more broadly?

Seth - The biomedical application is really clear here. So, we have characterized the first antibacterial gene in archaea and we think this work will open up and energize the pursuit of antibiotic discoveries in archaea which have arguably been a vastly under-tapped source for new antibiotic molecules. And as we race against the antibiotic resistance problem, well, we need all the help that nature's willing to give us. And so we want to pursue this thing a little further with the gene that we discovered. The broader question, the basic science question of how extensive is horizontal gene transfer? We're still learning and we were surprised to find the results that we did because we thought everything had been done on horizontal gene transfer that could possibly be done. But when we looked at this unusual case of the same gene moving between all types of life, we realize horizontal gene transfer was pushing its limits, at least in terms of our knowledge. So, we suspect it will be more to come. We suspect that antibiotic genes will be commonly transferred between different groups of life because of the universal pressure to deal with bacteria, either holding them at bay or turning them into mutualists, or just killing them outright to defend themselves against bacterial pathogens.